Discordance Between Capillary Refill Time and Oxygen Extraction Ratio in Septic Shock

Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorIstanbul University - Cerrahpasa

About this trial

In septic shock, restoring large-vessel (macrocirculatory) perfusion-reflected by a normal capillary refill time (CRT)-does not always mean that oxygen use at the tissue level has recovered. This mismatch, sometimes called loss of hemodynamic coherence, may be detectable by comparing CRT with the oxygen extraction ratio (O₂ER), a marker of how much oxygen the tissues are extracting from the blood. Patients whose CRT has normalized but whose O₂ER remains abnormal-either too high (suggesting oxygen delivery that is insufficient for demand) or too low (suggesting microcirculatory shunting)-are considered to have a "discordant" perfusion phenotype.

This prospective, single-center, observational cohort study aims to determine how often this CRT-O₂ER discordance occurs at the 6th hour of resuscitation in adult patients with septic shock, and whether it is associated with 28-day mortality. Approximately 100 consecutive adult patients diagnosed with septic shock (with pre-existing central venous and arterial catheters) will be followed. Clinical and laboratory measurements-including CRT, O₂ER, lactate, mottling score, and organ dysfunction scores-will be recorded at hours 0, 6, 12, and 24, with the main phenotype grouping performed at hour 6. The study is purely observational: CRT is a painless, non-invasive bedside measurement, and O₂ER is calculated from blood gas samples already drawn as part of routine care, so no additional interventions or blood draws are performed for research purposes.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 18 years

Diagnosis of septic shock according to the Surviving Sepsis Campaign (SSC) 2026 guideline

Presence of both a central venous catheter and an arterial line

Disqualifiers

Active bleeding

Ongoing extracorporeal membrane oxygenation (ECMO)

Raynaud phenomenon or significant peripheral vascular disease that makes capillary refill time measurement unreliable (e.g., critical ischemia, amputation, digital ulcer/necrosis, or inability to measure on the right index finger)

Death within the first 6 hours

Trial population

Consecutive adult patients (≥18 years) admitted to a single-center intensive care unit and diagnosed with septic shock according to the Surviving Sepsis Campaign (SSC) 2026 guideline, who already have a central venous catheter and an arterial line in place as part of their clinical care. Patients are enrolled from all admission sources (emergency department, ward, operating room, or external referral) and followed prospectively while receiving standard treatment. Patients with active bleeding, ongoing ECMO, conditions that make capillary refill time measurement unreliable (e.g., Raynaud phenomenon or significant peripheral vascular disease), death within the first 6 hours, or inability to obtain hour-6 CRT or blood gas measurements are not included.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Capillary refill time (CRT)

    Diagnostic test

    Non-invasive, standardized bedside measurement of capillary refill time on the right index finger.

  • Oxygen extraction ratio (O₂ER) assessment

    Diagnostic test

    Oxygen extraction ratio calculated as (SaO₂ - ScvO₂)/SaO₂ from routinely obtained arterial and central venous blood gases.

Treatment groups

100 Participants
are divided into 1 treatment group
Group A: septic schoc cohort2 interventions

Trial outcomes

Primary outcomes

1

Prevalence of the discordant CRT-O₂ER phenotype

Proportion of patients classified as having a discordant perfusion phenotype (normalized CRT ≤3 s with an abnormal O₂ER, i.e., \>30% or \<20%; combined Group 2a + Group 2b) at hour 6, reported with 95% confidence interval.

Time frame
At hour 6 of resuscitation (6 hours after vasopressor initiation)
2

28-day all-cause mortality

All-cause mortality at 28 days, and its association with the hour-6 perfusion phenotype.

Time frame
28 days from Hour 0 (vasopressor initiation)

Secondary outcomes

1

ICU length of stay

Duration of intensive care unit stay in days.

Time frame
Through study completion, up to 28 days
2

Hospital length of stay

Duration of hospital stay in days.

Time frame
Through study completion, up to 28 days
3

Duration of mechanical ventilation

Total days on mechanical ventilation (0 if never ventilated).

Time frame
Through study completion, up to 28 days
4

Time to vasopressor weaning

Time in hours to sustained vasopressor discontinuation (off ≥24 continuous hours), measured from Hour 0.

Time frame
From Hour 0 up to 28 days

Other outcomes

1

Diagnostic performance of the O₂ER threshold for mortality

Discriminative ability of O₂ER for 28-day mortality assessed by ROC analysis (area under the curve), with identification of the optimal cut-off and comparison to the literature threshold of 30%.

Time frame
Hour 6 measurement; mortality at 28 days
2

Inter-rater reliability of CRT measurement

Agreement of hour-6 CRT between two independent, blinded observers; intraclass correlation coefficient (ICC) for continuous values and Cohen's kappa for the ≤3 s normal/abnormal classification.

Time frame
Hour 6, first 20-30 patients

Sponsors and contacts

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Istanbul University - Cerrahpasa

Lead sponsor

Başakşehir Çam & Sakura City Hospital

Sponsor institution

Başakşehir Çam & Sakura City Hospital

Collaborator